Heart failure & cardiomyopathiesCohort study
Natural History and Clinical Outcomes of Patients With DSG2/DSC2 Variant-Related Arrhythmogenic Right Ventricular Cardiomyopathy
- Multicentre cohort study
- 5 countries in Europe and Asia
Authors' conclusion
ARVC attributable to variants in desmosomal cadherins mostly present with right ventricular or biventricular disease. Multiple variants are common in these patients and are associated with more frequent clinical penetrance, earlier onset of disease, and adverse clinical outcomes.
Study context
- Population
- DSG2 and DSC2 variant carriers (arrhythmogenic right ventricular cardiomyopathy (ARVC)), 5 countries in Europe and Asia254 with DSG2 variants
- Participants
- 271 participants
- Exposure
- Multiple-variant vs single-variant DSG2/DSC2 carriers
- Multiple variantsn = 78
- Outcome
- Phenotypic profile and clinical outcomes, focusing on HF and ventricular arrhythmia events
Main finding
As reported in the abstract
- Premature cardiac death before age 65 among definite ARVC (n=200)
- 41 (20.5%)
- Isolated RV dysfunction at presentation (n=81 with LVEF and RV FAC)
- 29 (35.8%)
- Biventricular dysfunction at presentation (n=81)
- 16 (19.8%)
- ARVC diagnosis, multiple vs single variants
- 96.2% versus 64.8%; P<0.001
- Severe LV dysfunction, multiple vs single variants
- 44.4% versus 22.1%; P=0.001
- RV dilation, multiple vs single variants
- 88.9% versus 55.8%, P<0.001
- Age at ARVC diagnosis, multiple vs single variants (years)
- 33 [18-49] versus 42 [27-54]; P<0.001
- End-stage HF more frequent in multiple-variant carriers
- P<0.001
- Malignant ventricular arrhythmias more frequent in multiple-variant carriers
- P=0.004
Observational data: associations, not effects.
Further findings
Age at disease onset, single-variant carriers with vs without intense exercise
- Younger at onset with intense physical exercise
- P = 0.001
End-stage HF, DSG2/DSC2 vs PKP2 patients
- Significantly higher risk in DSG2/DSC2 patients
- P < 0.001
Original publication
Natural History and Clinical Outcomes of Patients With DSG2/DSC2 Variant-Related Arrhythmogenic Right Ventricular Cardiomyopathy. Circulation. Published 24 March 2025. doi:10.1161/circulationaha.124.072226
Summarised from the published abstract; every number is checked against it